SAEY, DIDIER; PEPIN, VÉRONIQUE; BRODEUR, JULIE; LIZOTTE, JESSICA; GAGNON, PHILIPPE; LAVIOLETTE, LOUIS; NADREAU, ÉRIC; LEBLANC, PIERRE; MALTAIS, FRANÇOIS
Cycling exercise testing is commonly used in patients with chronic obstructive pulmonary disease (COPD) to assess exercise tolerance, develop safe and optimal exercise prescriptions, and evaluate the response to treatment (1). Although symptom-limited incremental exercise tests are probably the most commonly used, constant-workrate tests are gaining popularity because they are more sensitive than maximal tests to detect improvement in exercise tolerance following a variety of interventions (17). In fact, the endurance time to constant-workrate exercise is now recognized as a valid primary outcome in clinical trials evaluating the efficacy of bronchodilation in patients with COPD (13,15).
During cycling exercise tests, the expired gases are most commonly collected through a mouthpiece/noseclip combination to measure minute ventilation (VE), oxygen uptake (V̇O2), and CO2 excretion (V̇CO2). The mouthpiece is widely used because it is usually well tolerated and because of its convenience in minimizing air leaks. In the portion of patients who do not tolerate the mouthpiece, the facemask is one available alternative. Whether the mouthpiece and the facemask can be used interchangeably during a cycling exercise test in COPD is unclear. In fact, in patients with COPD, a number of physiological observations suggest that the choice of the interface could influence the tolerance to constant-workrate exercise as well as the ventilatory and gas exchange parameters. The use of a mouthpiece, through stimulation of upper-airway sensory receptors, often results in increased tidal volume and ventilation (19). Even a modest increase in the ventilatory requirement may have dramatic consequences on exercise tolerance in patients with COPD by inducing further dynamic hyperinflation and worsening the perception of dyspnea leading to premature exercise termination (14). Furthermore, when breathing though a mouthpiece, patients with COPD are prevented from using the pursed-lips breathing, a common strategy to delay expiration and improve dyspnea (10). The humidification of the inspiratory air is also compromised when breathing through a mouthpiece, and this could also influence breathing pattern (19). Lastly, potential differences in the dead space and resistance between the mouthpiece and the facemask could also influence breathing pattern during exercise. Although the global impact of these physiological processes on exercise tolerance, breathing pattern, the perception of dyspnea, and gas exchange is difficult to predict, we speculated that the use of the mouthpiece in patients with COPD, by stimulating ventilation and preventing pursed-lips breathing, would worsen dynamic hyperinflation and dyspnea, resulting in a reduced exercise tolerance when compared with the facemask.
The present study was therefore undertaken to compare the response to constant-workrate cycling exercise between the mouthpiece and the facemask in patients with COPD. The endurance time to constant-workrate exercise and the VE, V̇O2, V̇CO2, inspiratory capacity, dyspnea, and heart rate responses to constant-workrate exercise were therefore compared in 10 patients with COPD who performed two constant-workrate cycling exercise tests at 80% of the predetermined peak exercise capacity.
Ten sedentary males with spirometric evidence of chronic airflow limitation volunteered to participate in this study. The diagnosis of COPD was based on spirometry showing moderate to severe irreversible airflow obstruction (post bronchodilator forced expiratory volume in 1 s (FEV1) <70% predicted value, and FEV1/forced vital capacity (FVC) < 70%) (3) and current or past smoking history (>20 pack-year). Six patients were on tiotropium bromide, two patients on ipratropium bromide, six patients on long-acting β2-agonists, eight patients on as needed short-acting β2-agonists, eight patients on inhaled corticosteroids, and one on theophilline. Subjects were stable at the time of the study, and none suffered from cardiovascular, neurological, skeletal muscle, or any other condition that could alter their capacity to perform the exercise test. The research protocol was approved by the institutional ethics committee, and a signed informed consent was obtained from each subject.
Anthropometric measurements, pulmonary function testing, and a symptom-limited incremental cycling exercise test were done during the first visit. Within a week, subjects returned to the laboratory on two separate occasions to perform a constant-workrate cycling exercise at 80% of their peak workrate. These two exercise tests were separated by a 48-h resting period. Subjects were scheduled at the same time of day throughout the study. One test was performed with a mouthpiece and the other with a facemask. The order in which the interfaces were used was randomly determined to take into account any learning effect. Patients were asked to take their usual medication through the research protocol.
Pulmonary Function Testing
Standard pulmonary function tests including spirometry, lung volumes, and DLCO were obtained at the initial evaluation in all subjects according to previously described guidelines (2). Results were related to normal values of Knudson, Goldman, and Cotes (8,9,12).
Incremental Exercise Testing
During the initial evaluation, a symptom-limited incremental cycling exercise test was performed to determine peak exercise capacity. Briefly, subjects were seated on an electrically braked ergocycle (Quinton Corival 400; A-H Robins, Seattle, WA) and connected to the respiratory circuit through a mouthpiece. The exercise circuit consisted of a pneumotachograph, O2 and CO2 analyzers, and mixing chamber (Sensor Medics, Vmax Legacy, Yorba Linda, CA). After 5 min of rest, a progressive stepwise exercise test was performed up to the individual maximal capacity. Each exercise step lasted 1 min, and increments of 10 W were used. VE, V̇O2, and V̇CO2 were measured at rest and during exercise on a breath-by-breath basis.
Constant-Workrate Exercise Testing
After 5 min of rest, a constant-workrate cycling exercise was performed until exhaustion at a working intensity corresponding to 80% of the peak workrate achieved during the incremental exercise test. The workload was progressively adjusted to the targeted level over a 30-s period and was maintained until exhaustion. Patients were instructed to pedal at 60 rpm, and standardized encouragements were provided during exercise. One exercise was performed using a mouthpiece (adult medium silicone model no. 602073, Hans-Rudolph Inc., MO) and a noseclip, whereas the other one was performed with a facemask. Medium and large facemasks were available (adult medium and large model no. 8930, Hans-Rudolph Inc., MO). The facemasks were fitted over the mouth and nose using a netted headgear that straps onto each side of the mask. In each patient, the facemask size that offered the best comfort while avoiding or at least minimizing any air leak was used. To ensure similar resistances between the two types of interfaces, the openings of the mouthpiece and the facemasks had identical dimension and were directly connected to the same pneumotachograph (Sensormedic no. 775274). VE, V̇O2, and V̇CO2 were measured at rest and during exercise on a breath- by-breath basis. The perception of dyspnea was assessed at 2-min intervals during exercise using the modified Borg 10-point scale (6). Changes in operational lung volumes were derived from measurements of dynamic inspiratory capacity. Techniques for performing measurements have been previously reported (14,16). Inspiratory capacity was measured at rest, at 2-min intervals during exercise, and at end-exercise. Blood pressure was measured at 2-min intervals using an automated blood pressure monitor (Quinton Q412, Quinton, Botmhell, WA).
The V̇O2 on-kinetics was analyzed to determine the time constant and the amplitude of the response for this parameter. The breath-by-breath V̇O2 data, starting when the targeted workload was reached up to the end of exercise, were fitted by an exponential function in the form y = y0 + A(1 − exp−(t/τ)) where y0 is the baseline value, A the amplitude of the response, and τ the time constant. This first-order exponential model was adjusted with iterative techniques using SigmaPlot 2004 for Windows version 9.0 (Systat Software inc, Richmond, CA). Occasional V̇O2 data points obtained during inspiratory capacity maneuvers, swallowing, coughing, or sighing were omitted from the analysis (18).
Dead Space Determination
Dead space was determined for the mouthpiece and the facemasks by measuring the volume of water necessary to completely fill each interface. The dead space of the facemasks was measured while they were positioned and securely attached to the faces of three subjects. Using this method, the dead space of the mouthpiece was 58 mL, and those of the facemasks averaged 59 and 61 mL for the medium- and large-size facemasks, respectively.
Results are reported as mean ± SD. The duration of the constant-workrate exercises was defined as the endurance time. A paired t-test was used to compare the endurance time between the two interfaces. The agreement between the mouthpiece and facemask endurance time was assessed by the method described by Bland and Altman, where individual differences in endurance time between the two interfaces were plotted against the corresponding mean values. From these data, limits of agreement were then calculated (i.e., mean difference between the mouthpiece and the facemask ± 1.96 SD) (5). The level of agreement in the endurance time between the two interfaces was also evaluated using the intraclass correlation coefficient. The isotime (i.e., at the same absolute time) values for VE, V̇O2, V̇CO2, inspiratory capacity, dyspnea Borg score, and heart rate during submaximal exercise were compared using a two-way ANOVA, whereas the values at the end of exercise were compared using a paired t-test. One hundred percent isotime was defined as the shortest test between the two interfaces. This differed from the end-exercise analysis, which compared the end-exercise values obtained during both exercises. A statistical level of significance of 0.05 was used for all analyses.
Baseline characteristics (age, body mass index), pulmonary function tests, and peak exercise capacity of the patients are presented in Table 1. They had, on average, moderate airflow obstruction, mild hyperinflation, and mildly reduced peak exercise capacity (Table 1).
The endurance time averaged 335 ± 125 and 305 ± 112 s for the mouthpiece and facemask exercise, respectively (P = 0.22). The individual differences in the endurance time between the two interfaces plotted against the corresponding mean values in the 10 patients are shown in Figure 1. The agreement between the mouthpiece and the facemask was good, with a mean difference of 30 ± 74 s (P = 0.23), limits of agreement ranging from −115 to 175 s, and an intraclass correlation coefficient of 0.79. As shown in the Bland and Altman plot (Fig. 1), the differences in the endurance time between the mouthpiece and the facemask were spread around the mean difference, with no systematic trend observed as the endurance time to constant-workrate exercise increased.
FIGURE 1-Level of ag...Image Tools
Physiological values at isotime during submaximal exercise and at end-exercise are presented in Figure 2 and Table 2, respectively. The isotime values for VE, V̇O2, V̇CO2, inspiratory capacity, dyspnea Borg score, and heart rate during submaximal exercise were similar between the two interfaces (Fig. 2). However, the end-exercise values for VE, V̇O2, and V̇CO2 were significantly higher with the mouthpiece compared with the facemask (Fig. 3). The differences in end-exercise values for VE, V̇O2, and V̇CO2 between the mouthpiece and the facemask did not correlate with the endurance time during the facemask exercise. This suggests that the magnitude of the underestimation in these variables with the facemask was not related to the duration of the exercise. Patients became rapidly dyspneic during exercise and also demonstrated dynamic hyperinflation as indicated by the progressive decrease in inspiratory capacity (Fig. 2). The fall in oxygen desaturation was of small and similar magnitude during both tests (Table 2).
As shown in Figure 4, the V̇O2 data were well fitted by the monoexponential function in 8/10 patients (r = 0.85-0.95). In patient #2, the exercise duration was too short to allow the V̇O2 kinetics to show the typical exponential pattern. Patient #7 showed a highly variable V̇O2 tracing with the facemask, a pattern consistent with an intermittent leak. The V̇O2 data obtained in patient #3 were consistently lower with the facemask than with the mouthpiece during the entire exercise period, suggesting a continuous and stable leak with the facemask. It was decided to keep this patient in the V̇O2 kinetics analysis because her data were well fitted by the exponential function. In the eight patients included in this analysis, there was no statistically significant difference for A (1.01 ± 0.35 vs 0.98 ± 0.32 L·min−1 for the mouthpiece and facemask, respectively, P = 0.64) and τ (65.25 ± 35.45 vs 62.35 ± 23.98 s, for the mouthpiece and facemask, respectively, P = 0.69) between the two interfaces.
FIGURE 4-The kinetic...Image Tools
There was no significant difference for the locus of symptom limitation between the mouthpiece and the facemask. With the mouthpiece, three patients were limited by dyspnea, two by leg fatigue, and five by a combination of these two symptoms. The corresponding values for the facemasks were: six for dyspnea, two for leg fatigue, and two for both symptoms combined. Four patients expressed their preference for the mouthpiece, whereas the remaining patients preferred the facemask.
This study shows that either a mouthpiece or a facemask can be used with similar results to assess the endurance time to constant-workrate exercise in patients with COPD. Our initial hypothesis that the use of a facemask would allow patients to exercise for a longer period of time was not substantiated. We also found that the dyspnea, heart rate, and inspiratory capacity responses to constant-workrate exercise were similar between the two types of interfaces. Although VE, V̇O2, and V̇CO2 were similar between the mouthpiece and the facemask during most of the exercise period, the end-exercise values for these parameters were lower with the facemask. Lastly, it was possible to assess, with comparable results, the V̇O2 on-kinetics with the mouthpiece and the facemask, at least in the majority of patients in whom a good quality signal could be obtained. These observations are clinically relevant, given that the response to constant-workrate exercise is often used to assess the efficacy of various therapeutic interventions in patients with COPD (13,15).
There was no systematic difference in the endurance time in favor of one interface. Furthermore, the difference in endurance time between the mouthpiece and the facemask was within the range of the test-retest variability of the endurance time when two submaximal cycling exercises are performed in the same condition (15,20). This indicates that the choice of interface had marginal impact on the determination of endurance time. We therefore suggest that the interface should be selected based on individual preference. In this regard, it is no the worthy that 6 out of 10 patients expressed their preference for the facemask. The present results also have implications in the evaluation of the effects of different therapeutic strategies on exercise tolerance in COPD. Endurance time to constant-workrate exercise is gaining popularity as a primary outcome variable in clinical trials in patients with COPD (13). Based on the present findings, we suggest that although either interfaces could be used to measure the endurance time during exercise testing, it would be advisable to use the same interface in the pre- and posttreatment exercise evaluations as an attempt to minimize the technically related variability in the measurement of exercise tolerance.
VE, V̇O2, and V̇CO2 were higher at end-exercise when the mouthpiece was used. Two mechanisms can be proposed for this observation. The first possibility is that the ventilatory requirements could have been greater with the mouthpiece as a result of the stimulation of upper-airway sensory receptors or because of a greater dead space with this device. An alternative mechanism for the higher VE, V̇O2, and V̇CO2 end-exercise values with the mouthpiece is that there was a leak toward the end of exercise with the facemask. A number of reasons would support the latter mechanism. Stimulation of upper-airway sensory receptors would be expected as soon as the mouthpiece is in place (19), and not only at end-exercise, as was observed in the present study. Although anatomical and physiological dead space ventilation could not be calculated because arterial PCO2 was not measured, the similarity in the dead space of the two interfaces does not suggest that a difference in this parameter is a likely mechanism to explain why VE was higher at end-exercise with the mouthpiece compared with the facemasks. Differences in resistance between the two interfaces are an unlikely explanation for the higher VE, V̇O2, and V̇CO2 with the mouthpiece, given that the opening and connecting pneumotachographs were identical between the mouthpiece and the facemask. Lastly, the striking similarity in dyspnea and heart rate responses between the two exercise tests suggests that the higher VE, V̇O2, and V̇CO2 with the mouthpiece could be better explained by a technical reason (air leak with the facemask) than by an increased ventilatory and physiological requirements with the mouthpiece. The magnitude of the air leak was small and could therefore not be detected while the exercises were performed. We were careful to assure a tight seal with the facemask at rest, and this is probably why the VE, V̇O2, and V̇CO2 were almost identical for the larger part of the exercise duration. Toward the end of exercise, movements of the head and contractions of facial muscles resulting from the uncomfortable symptoms of exercise were commonly observed and were probably responsible for a small air leak around the facemask. The only notable exception to this was patient #3, in whom V̇O2 was consistently lower with the facemask than with the mouthpiece during the entire exercise period, suggesting a continuous and stable leak with the facemask.
Some of our results are at variance with findings from a previous study done in patients with chronic heart failure (4). These authors reported similar peak values for V̇O2 between the mouthpiece and the facemask during treadmill exercises in patients with chronic heart failure using interfaces similar to those used in the present study. We can only speculate on the reasons for these apparently discrepant results between their study and ours. One possible explanation is that less dyspnea perception at end exercise in patients with CHF, compared with COPD, would result in a more stable head in the former group and therefore in a better seal around the facemask.
The assessment of the V̇O2 response during exercise provides useful physiological information. Although exponential curve fitting from pooled V̇O2 data obtained during three to four bouts of exercise at the same intensity and under the same condition is best to reduce the variability of the V̇O2 on-kinetics analysis (18), this analysis can also be done from a single exercise test (7). The V̇O2 responses were well fitted by the monexponential function in the majority (8/10) of patients (Fig. 4), and the proportion of patients in whom this was not possible was comparable with previous reports (7). Values for the time constant and amplitude of the V̇O2 responses were also within the expected range for this disease (7) and were similar between the mouthpiece and the facemask. This suggests that the small difference in V̇O2 at the end of exercise between the mouthpiece and the facemask does not, on average, invalidate the V̇O2 on-kinetics analysis. However, some caution is warranted, because, as exemplified by patient #7, the absence of leak is essential to perform a reliable V̇O2 on-kinetics analysis.
In conclusion, the present study supports the use of the facemask as a valuable alternative to the mouthpiece in the determination of the endurance time to constant-workrate exercise in COPD. Caution is, however, warranted when interpreting the ventilatory and gas exchange parameters, particularly toward the end of exercise, where a leak may occur with the facemask.
The authors thank Serge Simard for his statistical assistance and Dr. Louis-Philippe Boulet and Dr. Richard Debigaré for helpful suggestions on the manuscript.
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